Perhaps some of the most important medical issues for years has been the health risks associated with cigarette smoking such as lung cancer, heart disease and emphysema, just to name a few. Moreover, new medical evidence regarding the dangers of exposure to second hand smoke by non-smokers has resulted in a societal conflict between the rights of smokers and those of the non-smoker. Despite attempts by many smokers to quit for both health reasons and peer pressure, their addiction to the nicotine element of cigarette smoke prevents their doing so as they have become both physiologically and psychologically dependant.
Hence, numerous products have been developed in the past to administer nicotine in a manner other than cigarette smoke so as to cure the craving while at the same time avoiding the deleterious effects of tars and carbon monoxide, inherent components of cigarette smoke. Nicotine containing pills have been developed, see U.S. Pat. No. 3,368,567 to Speer, however these have failed to successfully quell the nicotine craving since they are unable to achieve effectively high nicotine blood levels. A drug such as nicotine that is administered orally and absorbed by the stomach must first pass through the liver where most of it is deactivated. Nicotine-containing chewing gum encounters much of the same deactivation problems although some have found modest market success such as Nicorette.RTM., Lakeside Pharmaceuticals, Cincinnati, Ohio. These have also raised concerns regarding the causation of gum disease and their less than pleasant taste also affects patient compliance.
The object of the present invention is to provide a means, both economically and conveniently, for the administration of nicotine to the bloodstream of an addicted cigarette smoker by a means that will both avoid nicotine deactivation by the liver and will result in nicotine blood concentrations that will sufficiently satisfy the cravings of even the most ardent nicotine-dependant cigarette smoker. It is a further object of the present invention to provide a small, thin layered patch for the transdermal administration of nicotine to the blood stream in amounts sufficiently high enough to quell any craving for the drug so as to lessen or avoid any psychological or physiological discomfort by the addicted cigarette smoker. It is a further object of the present invention to provide a transdermal delivery system for nicotine composed of thin layered patches containing a range of concentrations of nicotine contained therein so that a gradual withdrawal from the substance can occur over time resulting in an eventually complete elimination of the addiction. Finally, it is an object of the present invention to provide a thin layered transdermal patch that can be discretely worn by the addict and yet contain sufficiently high concentrations of nicotine so as to be effective in reducing the addict's craving therefore.
The transdermal delivery of a drug to the blood system is well known in the art and much research has been carried out in this field. Most of this technology involves incorporation of the drug of interest into a matrix or carrier solvent which is held in a reservoir formed by a drug-impermeable backing and a drug permeable membrane that is placed in contact with the skin and through which the drug diffuses. See U.S. Pat. Nos. 4,655,768 to Marecki et al; 4,710,191 to Kwiatek et al. and 4,624,665 to Nuwayser et al. The permeable membranes are comprised of biologically useful polymers such as vinyl pyrrolidone and allylamine cross-linked with glutaraldehyde ('484), ethylene vinyl acetate copolymer ('665) and other acrylic copolymers in general. Some membranes are microporous in nature and allow for the diffusion of the active agent as microparticles. See U.S. Pat. Nos. 3,731,683 and 3,598,122 to Zaffaroni et al. and U.S. Pat. No. 4,743,249 to Loveland.
Most of the transdermal drug delivery patches or bandages known in the art are directed towards a controlled release of the drug for a prolonged period of time and unfortunately, the skin serves as an effective barrier against the permeation of most drugs into the human body. Delivery systems using a carrier solvent in a reservoir containment for the drug provide a steady flux of the drug across the membrane so long as undissolved drug remains in the reservoir. Matrix transdermal systems invariably provide a decreasing delivery of the drug with time as layers closer to the skin become depleted of the drug and those still containing the active are farther away and diffuse more slowly. Moreover, the need for a reservoir type containment system is bulky and often obvious to any casual observer. As a result, despite much research in the field only nitroglycerin, scopolamine, clonidine and estradiol have been commercially exploited in the transdermal area.
U.S. Pat. No. 4,822,617 to Parroy does disclose a transdermal drug delivery device that does away with the reservoir concept, but here the drug such as nitroglycerin, scopolamine etc., is incorporated in a lanolin petroleum-based ointment which is then spread about the surface of a laminar applicator containing recesses for containment of the drug. There is no permeable membrane and the ointment itself adheres the device to the skin. A strip of adhesive may also be used for greater security. Whereas other transdermal drug delivery systems known in the art have approached thinner laminar dimensions, they all require a three component structure and often require both a solid and liquid dispersion of the active to be administered. See U.S. Pat. No. 4 675,009 to Hynes et al. It is also evident from the prior art patents that the membrane, matrix or solvent employed is dependant upon the active as well.
Nicotine is not known for any therapeutic value and hence it has only been recently that work has been done whereby nicotine is incorporated in a transdermal delivery system as an aid to quit smoking.
U.S. Pat. No. 4,597,961 to Etscorn entitled "Transcutaneous Application of Nicotine" discloses a transdermal patch comprised of an occlusive backing and a reservoir which contains the nicotine dissolved in a carrier or solvent and a microporous membrane for diffusion of the nicotine to the skin. The rate of diffusion is low however, and due to the structure of the membrane and the manner in which the nicotine diffuses through to contact the skin, many patches would have to be worn during the course of a day in order to reach and maintain nicotine plasma levels sufficiently high enough to eliminate the craving for cigarettes. Moreover, the need for the reservoir containment system results in a bulky patch that is readily apparent to the casual observer.
A more recent development in this area is disclosed in U.S. Pat. No. 4,839,174 to Baker et al. wherein a transdermal nicotine patch is described. The patch is comprised of an impermeable backing layer, a polyurethane matrix in which liquid nicotine is dispersed and an adhesive which holds the patch in contact with the skin. The matrix is comprised of a polyether type polyurethane that is dissolved in a solvent such as tetrahydrofuran (THF). The nicotine is added from 10-20% by weight and the mixture cured onto the impermeable backing layer in a thickness of from 50-800 microns, depending on the dosage of nicotine desired An amine-resistant bioadhesive layer is then added for attachment of the patch to the skin. Since nicotine is a very volatile substance, the curing step of the nicotine/polyurethane mixture onto the impermeable backing layer results in losses of up to 30% of the nicotine through degradation and/or evaporation. Therefore, the initial nicotine loading content must be substantially higher so as to make up for this loss and consequently the procedure is quite expensive when carried out on the commercial level.
Japanese Patent Application No. 60-94209 to Tsuda et al and assigned to the Nitto Electrical Industrial Co. also discloses a nicotine-containing tape preparation comprised of a macromolecular substance with nicotine (2-10% w/w) incorporated therein. Suitable macromolecular substances are silicone, polyisoprene, methylene-butadiene and acrylic rubbers as well as polyvinyl alkyl ethers, alcohols and acetates. The process for incorporating the nicotine active into the macromolecular substance requires dissolving it into an organic solvent such as ethyl alcohol or chloroform. The required use of these volatile materials raises environmental concerns resulting in increased costs of manufacture and also poses health risks by exposure of the manufacturers to the fumes. Moreover, it is doubtful whether the low (2-10% w/w) concentration of nicotine incorporated into the tape preparation is sufficiently high enough to achieve serum blood nicotine levels that will cure the craving of the addict.